Pertuzumab 420mg/14ml solution for infusion vials

ImportanceAntibody-drug conjugates (ADCs), such as trastuzumab emtansine and trastuzumab deruxtecan, are effective in treating erb-b2 receptor tyrosine kinase 2 (ERBB2)-positive breast cancer (BC) that has progressed on prior ERBB2-targeted therapy, warranting evaluation of their cardiotoxic profiles.ObjectiveTo compare the incidence of cardiotoxic effects of ADCs vs standard-of-care chemotherapy regimens for ERBB2-positive locally advanced or metastatic BC.Data sourcesPubMed, ScienceDirect, Cochrane Library, and ClinicalTrials.gov databases were searched in December 2024 for studies published between 2000 and 2024.Study selectionThe included studies were (1) phase 3 clinical trials that investigated locally advanced or metastatic ERBB2-positive BC; (2) clearly defined left ventricular ejection fraction (LVEF) decrease or heart failure definitions; (3) clearly defined LVEF monitoring frequency by echocardiography or multigated acquisition scan; (4) included studies consisted solely of either trastuzumab emtansine, trastuzumab deruxtecan, or one of the first-line to fourth-line chemotherapy regimens for unresectable stage IV ERBB2-positive breast cancer per the 2025 National Comprehensive Cancer Network guidelines; and (5) clearly defined cardiovascular eligibility criteria.Data extraction and synthesisData from eligible studies were extracted by 3 reviewers. A random-effects model was used for the pooled analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.Main outcomes and measuresThe primary outcome was cardiotoxic effects, which were defined as the incidence of LVEF decrease. The pooled analysis was performed using logit-transformed proportions with the inverse variance method and a DerSimonian-Laird random-effects model for between-study variance, with Wilson score 95% CIs.ResultsIn this meta-analysis of 9538 patients, a pooled analysis demonstrated a 0.94% (95% CI, 0.56%-1.57%) incidence of LVEF decrease with trastuzumab emtansine, a 4.20% (95% CI, 2.91%-6.01%) incidence with trastuzumab deruxtecan, a 4.85% (95% CI, 3.73%-6.28%) incidence with trastuzumab plus chemotherapy, and a 5.52% (95% CI, 3.41%-8.83%) incidence with trastuzumab plus pertuzumab plus chemotherapy. A trim-and-fill analysis was used if evidence of publication bias was found.Conclusions and relevanceThis meta-analysis found that trastuzumab emtansine was associated with the lowest incidence of LVEF decrease, and trastuzumab deruxtecan, trastuzumab plus chemotherapy, and trastuzumab plus pertuzumab plus chemotherapy had similar incidences. More research is needed into the cardiotoxic effects of these therapies.

Abstract licence: CC BY

BackgroundHuman epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is an aggressive subtype that is associated with poorer outcomes. Neoadjuvant chemotherapy combined with trastuzumab has significantly improved prognosis, and the addition of pertuzumab has further enhanced the treatment response. Pathological complete response (pCR) is a reliable surrogate marker of long-term outcomes, and its achievement can inform surgical and adjuvant therapy decisions. While randomized controlled trials (RCTs) have demonstrated the benefits of dual HER2 blockade, real-world evidence (RWE) is critical for assessing treatment effectiveness in broader, more diverse populations.ObjectiveTo evaluate the impact of dual HER2 blockade with pertuzumab and trastuzumab compared to single-agent trastuzumab on pCR rates in early-stage HER2+ breast cancer using real-world data.MethodsA systematic review and meta-analysis were conducted using the PubMed, Embase, and Scopus databases from inception to February 28, 2025. Eligible studies were retrospective or prospective real-world investigations comparing neoadjuvant chemotherapy with trastuzumab alone versus trastuzumab plus pertuzumab. Data were extracted independently by two reviewers. Pooled odds ratios (ORs) for pCR, along with 95% confidence intervals (CIs), were calculated. The risk of bias was assessed using the Newcastle-Ottawa Scale.ResultsEighteen studies involving 8,651 patients met the inclusion criteria. The pooled odds ratio (OR) showed significantly higher pCR rates with dual HER2 blockade (OR: 1.81; 95% CI: 1.56-2.09), with no observed heterogeneity (I² = 0%). Subgroup analyses confirmed consistent findings across geographic regions and study characteristics. Publication bias was low, as supported by Egger's test (p = 0.37).ConclusionIn real-world settings, adding pertuzumab to neoadjuvant therapy significantly improves pCR rates in early-stage HER2+ breast cancer, aligning with RCT evidence. These findings support the broader adoption of dual HER2 blockade and highlight the need for further prospective real-world studies to refine treatment strategies for specific patient subgroups.

Abstract licence: CC BY